virginiamycin and Critical-Illness

Infection by Staphylococcus aureus in critically ill patients is usually associated with antimicrobial resistance and high mortality. A more effective antibiotic treatment is needed to replace older drugs that have limited efficacy. Novel substances active on methicillin-resistant Staphylococcus aureus, which are already available on the market or are still in development, are discussed in this review, with emphasis on nosocomial infections.. A number of new antibiotics are on the market (linezolid, quinupristin-dalfopristin, daptomycin) and there is good evidence regarding their efficacy, especially in methicillin-resistant Staphylococcus aureus infections. Linezolid is, to date, the best alternative in treating nosocomial pneumonia by methicillin-resistant Staphylococcus aureus. It is cost-effective; resistance levels are still very low but there are some concerns regarding its adverse events. Quinupristin-dalfopristin shows good activity in vitro but its efficacy in patients with pneumonia by methicillin-resistant Staphylococcus aureus is modest. Daptomycin is not recommended for pulmonary infections because of its reduced penetration in the lung tissue. Under current phase III trials in patients with nosocomial infections are tigecycline, ceftobiprole, and three new glycopeptides, all with particular activity against methicillin-resistant Staphylococcus aureus.. For the moment, there are limited and rather expensive therapeutic options for the infections by Staphylococcus aureus in the critically ill. No dramatic superiority of the new drugs in comparison to the standard therapies was observed in most of the clinical trials. Better results on the efficacy of the drugs under investigation are expected.

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Cephalosporins; Clinical Trials as Topic; Critical Illness; Daptomycin; Drug Resistance, Multiple, Bacterial; Glycopeptides; Humans; Linezolid; Lipoglycopeptides; Methicillin Resistance; Minocycline; Oxazolidinones; Staphylococcal Infections; Teicoplanin; Tigecycline; Virginiamycin

The growing incidence of infections due to Gram-positive multiresistant germs has stimulated research into new drugs endowed with broader activity, that are useful in case of infections unresponsive to common antibiotics. The case of a 28-year-old man infected with a methicillin resistant Staphylococcus aureus non responder to therapy with glycopeptide antibiotics is reported. At admission the patient presented a septic condition and required mechanical ventilation. Antibiotic therapy was immediately started with teicoplanin+meropenem. Blood culture and bronchial aspirate evidenced a methicillin resistant Staphylococcus aureus with high sensibility to glycopeptide antibiotics. Although this therapy produced a slight improvement in clinical condition and the patient was extubated, fever and leucocytosis associated with a BAL positive to methicillin resistant Staphylococcus aureus, in vitro susceptible to glycopeptides, persisted. Considering the possibility of a non-responder condition of the patient to glycopeptide antibiotics, quinupristin/dalfopristin was added. The streptogramin produced a quick improvement in clinical condition with resolution of sepsis and culture sterilization. The patient improved progressively and was discharged. In conclusion, in our experience the association quinupristin/dalfopristin was effective in the resolution of a critical methicillin resistant Staphylococcus aureus infection non responder to classical treatment with glycopeptide antibiotics that showed a high sensibility in vitro.

Topics: Adult; Anti-Bacterial Agents; Critical Illness; Humans; Male; Methicillin Resistance; Staphylococcal Infections; Thoracic Injuries; Tomography, X-Ray Computed; Virginiamycin; Wounds, Stab

Life-threatening infections with multiresistant gram-positive bacteria are increasing. Treatment with quinupristin/dalfopristin (Q-D) has turned out to be effective against such resistant pathogens.. We report on treatment of six patients on dialysis (four with additional liver injury) and of one renal graft recipient with normal renal function who had severe infections caused by multiresistant Staphylococus epidermidis (1/7), methicillin-resistant Staphylococcus aureus (4/7) and vancomycin-resistant Enterococcus faecium (2/7).. Six out of seven patients were cured by therapy with Q-D in adjusted doses lasting for 10 to 34 days. Pharmacokinetics of Q-D and its metabolites were determined and remained within the therapeutic range, despite a modest increase of all compounds at the presumed steady state. The concentrations of the metabolites of Q-D were clearly lower than the parent drugs, including those of quinupristin-conjugated derivatives, which has not been reported previously.. These preliminary results suggest that: a) neither quinupristin nor dalfopristin or its metabolites accumulated despite the long duration of treatment; b) no adjustment of the standard dosage regimen (three times 7.5 mg/kg/day) is necessary in end-stage renal disease.

Topics: Aged; Aged, 80 and over; Bacteremia; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterococcus faecium; Female; Follow-Up Studies; Gram-Positive Bacterial Infections; Humans; Kidney Failure, Chronic; Male; Methicillin Resistance; Middle Aged; Prospective Studies; Risk Assessment; Sampling Studies; Staphylococcal Infections; Treatment Outcome; Vancomycin Resistance; Virginiamycin